Download PDF
Thromb Haemost 1990; 63(01): 001-005
DOI: 10.1055/s-0038-1645675
Original Article
Schattauer GmbH Stuttgart

Dose-Response Studies on the Effect of n-3 Polyunsaturated Fatty Acids on Lipids and Haemostasis

E Berg Schmidt
The Departments of Clinical Chemistry and Clinical Immunology, Aalborg Hospital, Aalborg, Denmark
,
K Varming
The Departments of Clinical Chemistry and Clinical Immunology, Aalborg Hospital, Aalborg, Denmark
,
E Ernst
The Departments of Clinical Chemistry and Clinical Immunology, Aalborg Hospital, Aalborg, Denmark
,
P Madsen
The Departments of Clinical Chemistry and Clinical Immunology, Aalborg Hospital, Aalborg, Denmark
,
J Dyerberg
The Departments of Clinical Chemistry and Clinical Immunology, Aalborg Hospital, Aalborg, Denmark
› Author Affiliations
Further Information

Publication History

Received 30 May 1989

Accepted after revision 04 October 1989

Publication Date:
02 July 2018 (online)

Also available at
  PDF Download  Permissions and Reprints

Summary

We have studied the dose-response effects of dietary supplementation with n-3 polyunsaturated fatty acids (n-3 PUFA’s) on lipids and haemostasis. Ten healthy males were each given 1.3 g,4 g or 9 g of n-3 PUFA’s daily for 6-week periods. Bleeding time, HDL-cholesterol and plasminogen activator inhibitor increased with the dose of n-3 PUFA. Plasma fibrinogen and triglyceride levels were reduced in a dose-dependent fashion.

After ingestion of 1.3 g of n-3 PUFA’s plasma fibrinogen decreased from 9 to 7 μmol/l and HDL-cholesterol increased from 1.2 to 1.3 mmol/l. The bleeding time was prolonged from 5 to 6.5 min while triglyceride levels decreased from 1.2 to 0.9 mmol/l after ingestion of 4 g of n-3 PUFA’s. Dietary supplementation with the highest daily dose (9 g) reduced plasma levels of triglycerides, fibrinogen and von Willebrand factor, while bleeding time, plasminogen activator antigen, plasminogen activator inhibitor and the ratio of HDL-cholesterol to total cholesterol increased.

Keywords

n-3 fatty acids - Fish oil - Dose-response - Lipids - Haemostasis
 

  • References

  • 1 Kromhout D, Bosschieter EB, De Lezenne CoulanderC. The inverse relation between fish consumption and 20-year mortality from coronary heart disease. N Engl J Med 1985; 312: 1205-1209
    CrossrefPubMedSearch in Google Scholar
  • 2 Shekelle R, Missell L, Paul O, MacMillan-Schryock A, Stamler J. Fish consumption and mortality from coronary heart disease. N Engl J Med 1985; 313: 820
    CrossrefPubMedSearch in Google Scholar
  • 3 Norell SE, Ahlbom A, Feychting M, Pedersen NL. Fish consumption and mortality from heart disease. Br Med J 1986; 293: 426
    CrossrefPubMedSearch in Google Scholar
  • 4 Bjerregaard P, Dyerberg J. Mortality from ischaemic heart disease and cerebrovascular disease in Greenland. Int J Epidemiol 1988; 17: 514-519
    CrossrefPubMedSearch in Google Scholar
  • 5 Kromhout D. n-3 fatty acids and coronary heart disease: epidemiology from Eskimos to western populations. J Intern Med 1989; (Suppl. 225) suppl 1: 47-51
    PubMedSearch in Google Scholar
  • 6 Landymore RW, MacAuley M, Sheridan W, Cameron C. Cumulative experience with eicosapentaenoic acid and other platelet inhibitors for the prevention of intimal hyperplasia in autologous vein grafts. In: Proceedings of the AOCS Short Course on Polyunsaturated Fatty Acids and Eicosanoids Lands WE M. (ed) Biloxi; Mississippi: 1987: 342-345
  • 7 Weiner BH, Ockene IS, Levine PH, Cuenoud HF, Fischer M, Johnson BF, Daoud AS, Jarmolych J, Hosmer D, Johnson MH, Natale A, Vaudreuil C, Hoogasian JJ. Inhibition of atherosclerosis by cod liver oil in a hyperlipidaemic swine model. N Engl J Med 1986; 315: 841-6
    CrossrefPubMedSearch in Google Scholar
  • 8 Davis HR, Bridenstine RT, Vessilinovitch D, Wissler RW. Fish oil inhibits development of atherosclerosis in Rhesus monkeys. Arteriosclerosis 1987; 7: 441-9
    CrossrefPubMedSearch in Google Scholar
  • 9 Leaf A, Weber PC. Cardiovascular effects of n-3 fatty acids. N Engl J Med 1988; 318: 549-57
    CrossrefPubMedSearch in Google Scholar
  • 10 Dehmer GJ, Popma JJ, Van Den Berg EK, Eichhorn EJ, Prewitt JB, Campbell WB, Jennings L, Willerson JT, Schmitz JM. Reduction in the rate of early restenosis after coronary angioplasty by a diet supplemented with n-3 fatty acids. N Engl J Med 1988; 319: 733-40
    CrossrefPubMedSearch in Google Scholar
  • 11 Herold PM, Kinsella JE. Fish oil consumption and decreased risk of cardiovascular disease: a comparison of findings from animal and human feeding trials. Am J Clin Nutr 1986; 43: 566-98
    CrossrefPubMedSearch in Google Scholar
  • 12 Dyerberg J, Schmidt EB. n-3 fatty acids and cardiovascular disease - observations generated by studies in Greenland Eskimos. Wien Klin Wochenschr 1989; 101: 277-82
    PubMedSearch in Google Scholar
  • 13 Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 1972; 18: 499-502
    PubMedSearch in Google Scholar
  • 14 Kristensen SD, Schmidt EB, Andersen HR, Dyerberg J. Fish oil in angina pectoris. Atherosclerosis 1987; 64: 13-9
    CrossrefPubMedSearch in Google Scholar
  • 15 van Kuijk F JG M, Thomas DW, Stephens DJ, Dratz EA. Gaschromatography-mass spectrophotometry method for determination of phospholipids peroxides; transesterification to form methyl esters. J Free Radic Biol Med 1985; 1: 215-25
    CrossrefPubMedSearch in Google Scholar
  • 16 McCreary DK, Kossa WC, Ramachandran S, Kurtz RR. A novel and rapid method for gas chromatography: Application to the determination of the fatty acids of edible fats and oils. J Chromatogr Sci 1978; 16: 329-31
    CrossrefPubMedSearch in Google Scholar
  • 17 Schmidt EB, Kristensen SD, Sørensen PJ, Dyerberg J. Antithrombin III and protein C in stable angina pectoris - influence of dietary supplementation with polyunsaturated fatty acids. Scand J Clin Lab Invest 1988; 48: 469-73
    PubMedSearch in Google Scholar
  • 18 Sanders TA B, Roshanai F. The influence of different types of ω-3 polyunsaturated fatty acids on blood lipids and platelet function in healthy volunteers. Clin Sci 1983; 64: 91-9
    CrossrefPubMedSearch in Google Scholar
  • 19 Von Schacky C, Fischer S, Weber PC. Long-term effects of dietary marine w-3 fatty acids upon plasma and cellular lipids, platelet function, and eicosanoid formation in humans. J Clin Invest 1985; 76: 1626-31
    CrossrefPubMedSearch in Google Scholar
  • 20 Simons LA, Hickie JB, Balasubramaniam S. On the effects of dietary n-3 fatty acids (Maxepa) on plasma lipids and lipoproteins in patients with hypcrlipidaemia. Atherosclerosis 1985; 54: 75-88
    CrossrefPubMedSearch in Google Scholar
  • 21 Schcctman G, Kissebah AH. Effect of marine lipid concentrate dose on plasma lipoproteins in hypertriglyceridemic subjects. Clin Res 1987; 35: 370 A
    PubMedSearch in Google Scholar
  • 22 Schectman G, Kaul A, Kissebah AH. Effect of fish oil concentrate on HDT-cholesterol and apo A-1 levels in hypertriglyceridemic subjects. Arteriosclerosis 1987; 7: 508 a
    PubMedSearch in Google Scholar
  • 23 Høstmark AT, Bjerkedal T, Kierulf P, Flaten H, Ulshagen K. Fish oil and plasma fibrinogen. Br Med J 1988; 297: 180-1
    CrossrefPubMedSearch in Google Scholar
  • 24 Saynor R, Gillott T. Fish oil and plasma fibrinogen. Br Med J 1988; 297: 1196
    PubMedSearch in Google Scholar
  • 25 Meade TW, Brozovic M, Chakrabarti RR, Haines AP, Imeson JD, Mellows S, Miller GJ, North WR S, Stirling Y, Thompson SG. Haemostatic function and ischaemic heart disease: Principal results of the Northwick Park Heart Study. Lancet 1986; ii: 533-7
    PubMedSearch in Google Scholar
  • 26 Wilhelmsen L, Svardsudd K, Korsan-Bengtsen K, Larsson B, Welin L, Tibblin G. Fibrinogen as a risk factor for stroke and myocardial infarction. N Engl J Med 1984; 311: 501-5
    CrossrefPubMedSearch in Google Scholar
  • 27 Kannel WB, Wolf PA, Castelli WP, D’Agostino RB. Fibrinogen and risk of cardiovascular disease. JAMA 1987; 258: 1183-6
    CrossrefPubMedSearch in Google Scholar
  • 28 Barcelli U, Glas-Greenwalt P, Poliak VE. Enhancing effect of dietary supplementation with Ω-3 fatty acids on plasma fibrinolysis in normal subjects. Thromb Res 1985; 39: 307-12
    CrossrefPubMedSearch in Google Scholar
  • 29 Emeis JJ, Houwelingen AC v, Hoogen C MV D, Hornstra G. A moderate fish Intake increases plasminogen activator inhibitor type-1 in human volunteers. In:Houwelingen A C v, Fish against Thrombosis? (Thesis) 1988
    PubMedSearch in Google Scholar
  • 30 Hansen J-B, Olsen JO, Wilsgård L, Østerud B. Effects of dietary supplementation with cod liver oil on monocyte thromboplastin synthesis, coagulation and fibrinolysis. J Intern Med 1989; 225 suppl (Suppl. 01) 133-9
    CrossrefPubMedSearch in Google Scholar
  • 31 Smith P, Arnesen H, Opstad T, Dahl KH, Eritsland J. Influence of highly concentrated n-3 fatty acids on serum lipids and hemostatic variables in survivors of myocardial infarction receiving either oral anticoagulants or matching placebo. Thromb Res 1989; 53: 467-74
    CrossrefPubMedSearch in Google Scholar
  • 32 Schmidt EB, Ernst E, Varming K, Pedersen JO, Dyerberg J. The effect of n-3 fatty acids on lipids and hemostasis in patients with type II a and type IV hyperlipidaemia. Thromb Haemostas 1989; 62: 797-801
    PubMedSearch in Google Scholar
  • 33 Lagarde M, Croset M, Vericel E, Calzada C. Effects of small concentrations of eicosapentaenoic acid on platelets. J Intern Med 1989; 225 suppl (Suppl. 01) 177-9
    CrossrefPubMedSearch in Google Scholar
  • 34 Davidson DM, Gold KV. Cardiovascular effects of n-3 fatty acids. N Engl J Med 1988; 321: 580
    PubMedSearch in Google Scholar
  • 35 Bang HO, Dyerberg J, Nielsen AB. Plasma lipid and lipoprotein pattern in Greenlandic west coast Eskimos. Lancet 1971; i: 1143-6
    PubMedSearch in Google Scholar
  • 36 Dyerberg J, Bang HO. Haemostatic function and platelet polyunsaturated fatty acids in Eskimos. Lancet 1979; ii: 433-5
    PubMedSearch in Google Scholar
  • 37 Fischer S, Weber PC, Dyerberg J. The prostacyclin/thromboxane balance is favourably shifted in Greenland Eskimos. Prostaglandins 1986; 32: 235-41
    CrossrefPubMedSearch in Google Scholar
  • 38 Siess W, Scherer B, Bohling B, Roth P, Kurzman I, Weber PC. Platelet-membrane fatty acids, platelet aggregation, and thromboxane formation during a mackerel diet. Lancet 1980; i: 441-4
    PubMedSearch in Google Scholar
  • 39 Goodnight SH, Harris WS, Connor WE. The effects of dietary ω-3 fatty acids on platelet composition and function in man: A prospective, controlled study. Blood 1981; 58: 880-885
    PubMedSearch in Google Scholar
  • 40 Harris WS, Connor WE, McMurry MP. The comparative reductions of the plasma lipids and lipoproteins by dietary polyunsaturated fats: Salmon oil versus vegetable oils. Metabolism 1983; 32: 179-184
    CrossrefPubMedSearch in Google Scholar
  • 41 Lorenz RL, Spengler U, Fischer S, Duhm J, Weber PC. Platelet function, thromboxane formation and blood pressure control during supplementation of the western diet with cod liver oil. Circulation 1983; 67: 504-511
    CrossrefPubMedSearch in Google Scholar
  • 42 Illingworth DR, Harris WS, Connor WE. Inhibition of low density lipoprotein synthesis by dietary omega-3 fatty acids in humans. Arteriosclerosis 1984; 4: 270-275
    CrossrefPubMedSearch in Google Scholar
  • 43 Phillipson BE, Rothrock DW, Connor WE, Harris WS, Illingworth DR. Reduction of plasma lipids, lipoproteins, and apoproteins by dietary fish oils in patients with hypertriglyceridemia. N Engl J Med 1985; 312: 1210-1216
    CrossrefPubMedSearch in Google Scholar
  • 44 Knapp HR, Reilly IA G, Alessandrini P, Fitzgerald GA. In vivo indexes of platelet and vascular function during fish-oil administration in patients with atherosclerosis. N Engl J Med 1986; 314: 937-942
    CrossrefPubMedSearch in Google Scholar
  • 45 Knapp HR, Fitzgerald GA. The antihypertensive effects of fish oil. N Engl J Med 1989; 320: 1037-1043
    CrossrefPubMedSearch in Google Scholar
  • 46 Schmidt EB, Sørensen PJ, Ernst E, Kristensen SD, Pedersen JO, Dyerberg J. Studies on coagulation and fibrinolysis in Greenland Eskimos. Thromb Res (in press)
    PubMed